Aortic dissection has the primary pathology of an intimal tear that penetrates the aortic media, as is illustrated in FIG. 2. This entry tear often occurs at sites of greatest wall tension, usually within a few centimeters of the aortic valve on the right lateral wall of the ascending aorta. This is commonly referred to as type A dissection. Blood at high pressure then splits or dissects the aortic media to form a false channel or lumen that runs alongside the true lumen, as is illustrated in FIG. 3. Aortic dissection is one of the most common and lethal illness conditions involving the aorta. Rapid diagnosis as well as an appropriate therapy is essential for survival of the patients. Acute type A dissection, which involves the ascending aorta, normally has a mortality of 1% to 2% per hour during the first 48 hours after initiation. Further, it can quickly extend towards the heart and cause death by cardiac tamponade, blockage of coronary arteries or progress more distally to occlude aortic arch vessels.
Consequently, without surgical therapy, acute type A aortic dissection is nearly invariably lethal with an expected 90-day mortality of 70% to 90%. With modern medical management, the survival rates are greater, but the mortality rate is still above 50%. Surgery includes extra corporal circulation with cerebral perfusion and implantation of a composite graft in the ascending aorta with or without re-implantation of coronary arteries and the aortic valve.
It has been shown that the risk of mortality from surgery for acute type A aortic dissection is high with increasing age. It is published figures of 45% for patients 80 to 84 years of age and 50% for those 85 years or older. As a consequence many patients are not treated with surgery, especially in the presence of high age and/or co-morbidities.
It is obvious that a less traumatic but still invasive alternative would be of importance for many cases. Endovascular treatment is often not possible because of the anatomical restrictions of securing a traditional stent graft within the ascending aorta. Furthermore, the dissection usually involves the aortic arch from which the arteries to the brain take off. Permanent coverage of this area carries continuous lethal danger. The lethal danger consists of the risk of clot formation on the stent material with the release of emboli to the brain. Furthermore, clot formation at numerous locations on a stent placed across aortic arch vessels might reduce the blood supply to the brain. Both risks will increase with increased time of presence of the stent, making permanent stents non-suitable for this type of treatment. The alternative of having a permanent stent combined with lifelong and aggressive anti-coagulation carries high risks of bleeding complications. Cerebral hemorrhage with lethal outcome is a well-known side effect already with normal use of anti-coagulation in a lifelong perspective.
Even if the mortality rate is highest with acute type A dissections, also type B dissections may need interventions. The type B dissection is defined to have its entry to the false lumen distal to the left subclavian artery. It is usually treated conservatively but if indications such as intractable pain, a rapidly expanding aortic diameter, development of periaortic or mediastinal hematoma as signs of imminent aortic rupture are present, an intervention is often required. Often in these cases the type B dissection involves important side branches of the aorta. Sometimes the dissection extends into such side branches, which may then need a treatment of its own.
A dissection occurs in the media of the aortic wall. It is well-known that injury to this vessel wall layer induces an inflammatory response with neutrophil infiltration, fibrin formation, and smooth muscle cell proliferation. It stimulates a wound-healing mechanism. Spontaneous healing of aortic dissection is however very rare. Probably, because a flow of blood keeps the separated membrane apart from its original position. The placement of a permanent stent (in type B dissections) to approach the separated membrane to the media is known to facilitate healing of the dissection and sometimes of the entire aorta, including abdominal segments. The reason why permanent stents can be used in certain cases in dissections type B is that the extension of the dissection sometimes only includes the descending thoracic aorta, which does not have any crucial side branches. As soon as the visceral arteries are included or if a retrograde dissection occurs into the aortic arch, permanent stents are less suitable.
It is obvious that a temporary attachment of the separated membrane to the media during the healing process of the dissection would be an alternative for type A dissections and also for type B dissections with side branch involvement or for isolated important single branches. Temporary attachment would be preferred, because permanent coverage of the aortic arch and important side-branches carry too high risk. Such a suggested temporary approach might need simultaneous and aggressive anticoagulation therapy.
There is therefore a need for a removable stent that can be used for such treatments.
Another medical area of interest is temporary and local application of very powerful drugs or irradiation. As examples: it has been shown in clinical studies in head and neck cancer that the combination of cisplatin/epinephrine placed locally in an injectable gel may reduce the size of solid tumors, improve quality of life, and produce fewer traditional chemotherapy-related side effects than intravenous chemotherapy. Intralymph nodal injection or intraperitoneal administration of mitomycin C carried by small activated carbon particles seems to improve the survival rates and might be able to treat peritoneal metastases in gastric cancer. These treatments lack the possibility to regulate the timeframe, which of course influences, the dosages applied. Internal radiation for uterine cancer is one example of combined local application and regulated time for the treatment. In this treatment tiny tubes containing a radioactive substance are inserted through the vagina and left in place for a planned time period. No treatment is yet available for cancer in the gastro-intestinal tract including the esophagus or in the hepatico-pancreatico-biliar system with the characteristics of being local and where the time for treatment is under control. The same is true for parenchymal cancers such as pulmonary, hepatic and brain cancer. There are a number of oncological substances and potentially specific irradiation agents, which have shown partial effect against cancer. The use of these and similar factors is limited by side-effects when delivered systemically. The dosage that reaches the target area will thereby be reduced and so will the effect.
The use of stents in the treatment of e.g. arterial stenosis is well known in the art. The majority of stents used today are for permanent use. However, stents for temporary use are also described in the prior art. A temporary stent can either be removable or biodegradable so that it is degraded after a certain amount of time. Biodegradable stents, such as e.g. disclosed in WO9315787, US2007055364 and 6981987, have the advantage that they do not require an invasive removal procedure for non-permanent use. However, when using biodegradable stents it is not possible to control the treatment time in detail since the degradation of the stent is a slow chemical process. This has hindered the use of biodegradable stents for the treatment of e.g. aortic dissection where a short duration of treatment is needed to reduce the risk of embolism and to keep the duration of aggressive anticoagulation therapy at a minimum for safety reasons. The time for treatment if these stents carry either chemotherapy or irradiation cannot be precisely controlled. Polymeric biodegradable stents have demonstrated other limitations. Their mechanical strength is lower than e.g. metallic stents. The polymer alone has a limited mechanical performance and a recoil rate of approximately 20%, which requires thick struts that impede their profile and delivery capabilities. Further, they are associated with a significant degree of local inflammation. This reaction combined with the slow bioabsorption rate may result in restenosis. Also, these stents are radiolucent, which may impair accurate positioning and makes it impossible to control the position after delivery. Furthermore, it is difficult to deploy the stent smoothly and precisely without fluoroscopic visualization. The possibility to control the position is especially important if a stent carries potent treatment modalities.
Removable stents have the advantage that they can be removed at any time, either when the treatment is finalized or if the treatment needs to be terminated or relocated for any other reason. Unfortunately, the removable stents in the art all require an invasive removal procedure, using e.g. an endoscope, to contact the stent at the treatment site and then remove the stent from the treatment site. This removal procedure is associated with risk, especially around the treatment site where the tissue is likely to be extra sensitive for this type of manipulation because of the treated condition. This is of great importance in e.g. aortic dissections where the vascular wall just has undergone a reparative process that could risk being reversed by this type of manipulation. Also advanced cancer has bleeding tendencies and consists of fragile tissue, which makes it preferred to avoid any local manipulation. There is at present no available stent which enables removal in a non-invasive or minimally invasive manner.
Some examples of previously known removable stents will now be discussed briefly.
In US2008071287 a stent recovery apparatus that recovers a stent from a body cavity, e.g. the esophagus, is described. The device is inserted from outside the body into the body cavity where it catches one end of the stent before the removal can be initiated. When the proximal end of the stent is subjected to a pulling force the loops unwind and the stent can be removed in the form of a wire. The described stent and stent recovery apparatus are not suitable for the treatment of aortic dissections for several reasons. Firstly, a blood vessel such as the aorta is not a body cavity. Secondly, and more importantly, the stent does not have a high enough porosity to permit blood flow to important blood vessels from the aorta through the sides of the stent, an essential function if a stent is to be used in aortic dissections type A; the sparsity is also limited which also is a hindrance to a good blow flow through the surface into a side branch artery. Furthermore, the invasive removal procedure described in the application would risk the reversal of e.g. the healed aortic dissection since the inside of the blood vessel is very fragile at the treatment site or induce bleedings in well circulated cancer tissue alternatively perforations through the cancer tissue. Further, the stents disclosed in US2008071287 are very fragile, and there is a severe risk of uncontrolled disintegration at any location throughout its length during use.
U.S. Pat. No. 5,514,176 and WO 2005/058201 describe removable stents made as coils with adjacent loops packed tightly together. For removal of the stent, a surgical instrument, e.g. a forceps, is introduced from outside the body and contacts the proximal end of the stent, for detachment of adjacent loops from one another. These stents are substantially imperforate and virtually no blood can pass through the sides of the stent. This very limited permissiveness of blood flow through the sides of the stent makes the stent unsuitable for treatment of aortic dissections. In addition to the need for an invasive removal procedure, the relatively rigid and wide strand resulting from the detachment procedure is not particularly suitable for convenient removal. Further, these stents uses wires attached to an implant, making the stents rather costly and difficult to produce. Further, this increases the risk of separation between the wire and the implant, which would complicate the removal of the implant.
Another type of removable stents uses one or more wires wrapped around the implant, and useable to compress the implant, thereby reducing its diameter, for removal. Such stents are e.g. disclosed in U.S. Pat. No. 7,252,680, US2006276887 and US2005080480. However, with this type of removable stents, it is not possible to remove the implant without using an invasive removal procedure such as a new endoscopic procedure. Also, the diameter of the stent is still relatively large, even in the compressed state. Further, the stents of this type are also relatively complicated and costly to produce, and there is also a risk of separation between the collapsing elements and the implant, which would complicate the removal of the implant.
Stents delivering drugs, so called drug-eluting stents, are also known in the art and have been used since 2003, see e.g. U.S. Pat. No. 5,383,928, US2005256075, US2008138375 and US2008146489. Initially, drug eluting stents contained cytostatic compounds, that is, compounds that curtailed the proliferation of cells that resulted in restenosis. These stents all have the drawback of not being able to remove, which makes it impossible to regulate the time for treatment, including disables the possibility to interrupt the treatment in the case of side-effects.
In WO9951299 a stent for treatment of e.g. cancer and restenosis is described. In one embodiment, a composition having a radioactivable isotope incorporated into a matrix material is formed into a medical device, e.g. a stent. However, the stent is not constructed so that it can be removed, instead a low dose of a radioactive isotope with a short half-life is used to limit the duration of the treatment. Further, there is no possibility of controlling both the treatment site and the duration of the treatment.
There is therefore still a need for an improved removable stent.